Assessment of poly(methacrylic acid-co-N-vinyl pyrrolidone) as a carrier for the oral delivery of therapeutic proteins using Caco-2 and HT29-MTX cell lines
Hydrogels of poly(methacrylic acid‐co‐N‐vinyl pyrrolidone) were synthesized and evaluated for their use as carriers for oral protein delivery. Insulin loading efficiencies were determined to be near 90% for carriers crosslinked with ethylene glycol dimethacrylate with corresponding weight incorporat...
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Veröffentlicht in: | Journal of biomedical materials research. Part A 2010-02, Vol.92A (2), p.504-512 |
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description | Hydrogels of poly(methacrylic acid‐co‐N‐vinyl pyrrolidone) were synthesized and evaluated for their use as carriers for oral protein delivery. Insulin loading efficiencies were determined to be near 90% for carriers crosslinked with ethylene glycol dimethacrylate with corresponding weight incorporation levels near 12%. Although no insulin was released in gastric conditions, as desired, near instantaneous release occurred when the pH was raised to values typical of the intestinal area. Cytocompatibility studies with Caco‐2 and Caco‐2/HT29‐MTX cultures demonstrated that microparticles did not elicit toxic effects at concentrations up to 5.0 mg/mL. Insulin transport studies revealed that the carriers did not disrupt the cell layer and thus did not change the insulin permeability in the apical‐to‐basolateral direction. Therefore, microparticles of this system were best suited for oral delivery of therapeutic agents that do not require transport facilitation. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010 |
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Insulin loading efficiencies were determined to be near 90% for carriers crosslinked with ethylene glycol dimethacrylate with corresponding weight incorporation levels near 12%. Although no insulin was released in gastric conditions, as desired, near instantaneous release occurred when the pH was raised to values typical of the intestinal area. Cytocompatibility studies with Caco‐2 and Caco‐2/HT29‐MTX cultures demonstrated that microparticles did not elicit toxic effects at concentrations up to 5.0 mg/mL. Insulin transport studies revealed that the carriers did not disrupt the cell layer and thus did not change the insulin permeability in the apical‐to‐basolateral direction. Therefore, microparticles of this system were best suited for oral delivery of therapeutic agents that do not require transport facilitation. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010</description><identifier>ISSN: 1549-3296</identifier><identifier>ISSN: 1552-4965</identifier><identifier>EISSN: 1552-4965</identifier><identifier>DOI: 10.1002/jbm.a.32395</identifier><identifier>PMID: 19213059</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Administration, Oral ; Algorithms ; Assessments ; Biological and medical sciences ; Caco-2 Cells ; Carriers ; cell culture ; Cell Survival - drug effects ; Crosslinking ; cytocompatibility ; Drug Carriers ; Drug Delivery Systems ; Gastric Mucosa - metabolism ; General pharmacology ; Hormones. Endocrine system ; HT29 Cells ; Humans ; Hydrogels ; Hypoglycemic Agents - administration & dosage ; Hypoglycemic Agents - chemistry ; Insulin ; Insulin - administration & dosage ; Insulin - chemistry ; Intestinal Mucosa - metabolism ; Kinetics ; Materials Testing ; Medical sciences ; Methylmethacrylates - chemistry ; Microparticles ; Nanoparticles ; oral delivery ; Pharmaceutical technology. Pharmaceutical industry ; Pharmacology. Drug treatments ; Povidone - chemistry ; Proteins ; Proteins - administration & dosage ; Reproduction ; Transport</subject><ispartof>Journal of biomedical materials research. 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Part A</title><addtitle>J. Biomed. Mater. Res</addtitle><description>Hydrogels of poly(methacrylic acid‐co‐N‐vinyl pyrrolidone) were synthesized and evaluated for their use as carriers for oral protein delivery. Insulin loading efficiencies were determined to be near 90% for carriers crosslinked with ethylene glycol dimethacrylate with corresponding weight incorporation levels near 12%. Although no insulin was released in gastric conditions, as desired, near instantaneous release occurred when the pH was raised to values typical of the intestinal area. Cytocompatibility studies with Caco‐2 and Caco‐2/HT29‐MTX cultures demonstrated that microparticles did not elicit toxic effects at concentrations up to 5.0 mg/mL. Insulin transport studies revealed that the carriers did not disrupt the cell layer and thus did not change the insulin permeability in the apical‐to‐basolateral direction. Therefore, microparticles of this system were best suited for oral delivery of therapeutic agents that do not require transport facilitation. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010</description><subject>Administration, Oral</subject><subject>Algorithms</subject><subject>Assessments</subject><subject>Biological and medical sciences</subject><subject>Caco-2 Cells</subject><subject>Carriers</subject><subject>cell culture</subject><subject>Cell Survival - drug effects</subject><subject>Crosslinking</subject><subject>cytocompatibility</subject><subject>Drug Carriers</subject><subject>Drug Delivery Systems</subject><subject>Gastric Mucosa - metabolism</subject><subject>General pharmacology</subject><subject>Hormones. Endocrine system</subject><subject>HT29 Cells</subject><subject>Humans</subject><subject>Hydrogels</subject><subject>Hypoglycemic Agents - administration & dosage</subject><subject>Hypoglycemic Agents - chemistry</subject><subject>Insulin</subject><subject>Insulin - administration & dosage</subject><subject>Insulin - chemistry</subject><subject>Intestinal Mucosa - metabolism</subject><subject>Kinetics</subject><subject>Materials Testing</subject><subject>Medical sciences</subject><subject>Methylmethacrylates - chemistry</subject><subject>Microparticles</subject><subject>Nanoparticles</subject><subject>oral delivery</subject><subject>Pharmaceutical technology. Pharmaceutical industry</subject><subject>Pharmacology. Drug treatments</subject><subject>Povidone - chemistry</subject><subject>Proteins</subject><subject>Proteins - administration & dosage</subject><subject>Reproduction</subject><subject>Transport</subject><issn>1549-3296</issn><issn>1552-4965</issn><issn>1552-4965</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkk9v1DAQxSMEomXhxB35gihCWfwnduILUllBC2qLBAvlZk0cp-vijYOdXchn4cviZZcFLuVky_7Nm3mjl2UPCZ4SjOnz63o5hSmjTPJb2SHhnOaFFPz25l7InFEpDrJ7MV4nWGBO72YHRFLCMJeH2Y_jGE2MS9MNyLeo9248WpphATqMzmoE2ja59vlFvrbd6FA_huCdbXxnniKICJCGEKwJqPUBDQuDfACHGuPs2oRxo5keA_RmNSS5PvjB2C6iVbTdFZpBkqYIugadzqnMz-efkTbOIWc7E-9nd1pw0TzYnZPs4-tX89lpfvbu5M3s-CzXvCp5zqkgnGje1BoIZrUocUslVDWtNOZFIbho0254SwFkCSWndcPLgpO21VS0NZtkL7a6_apemkanXSQPqg92CWFUHqz696ezC3Xl14rhgpKCJYEnO4Hgv65MHNTSxo0P6IxfRVVVDNMSE_F_UkheUcFpIo9uJIkoCS0wkTKhz7aoDj7GYNr96ASrTURUiogC9SsiiX70t9s_7C4TCXi8AyBqcG2ATtu452jqylmyNMnIlvtmnRlv6qnevjz_3Tzf1tg4mO_7GghflChZydXlxYm6_FC-rzD7pEr2E5IO4-A</recordid><startdate>201002</startdate><enddate>201002</enddate><creator>Carr, Daniel A.</creator><creator>Peppas, Nicholas A.</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley-Blackwell</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7SR</scope><scope>7TB</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>F28</scope><scope>FR3</scope><scope>JG9</scope><scope>L7M</scope><scope>7QO</scope><scope>P64</scope><scope>5PM</scope></search><sort><creationdate>201002</creationdate><title>Assessment of poly(methacrylic acid-co-N-vinyl pyrrolidone) as a carrier for the oral delivery of therapeutic proteins using Caco-2 and HT29-MTX cell lines</title><author>Carr, Daniel A. ; Peppas, Nicholas A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5875-526151c5dbca103b670f29a8b28c0544656f3955f2aa97a752bd57451ffc26fb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Administration, Oral</topic><topic>Algorithms</topic><topic>Assessments</topic><topic>Biological and medical sciences</topic><topic>Caco-2 Cells</topic><topic>Carriers</topic><topic>cell culture</topic><topic>Cell Survival - drug effects</topic><topic>Crosslinking</topic><topic>cytocompatibility</topic><topic>Drug Carriers</topic><topic>Drug Delivery Systems</topic><topic>Gastric Mucosa - metabolism</topic><topic>General pharmacology</topic><topic>Hormones. Endocrine system</topic><topic>HT29 Cells</topic><topic>Humans</topic><topic>Hydrogels</topic><topic>Hypoglycemic Agents - administration & dosage</topic><topic>Hypoglycemic Agents - chemistry</topic><topic>Insulin</topic><topic>Insulin - administration & dosage</topic><topic>Insulin - chemistry</topic><topic>Intestinal Mucosa - metabolism</topic><topic>Kinetics</topic><topic>Materials Testing</topic><topic>Medical sciences</topic><topic>Methylmethacrylates - chemistry</topic><topic>Microparticles</topic><topic>Nanoparticles</topic><topic>oral delivery</topic><topic>Pharmaceutical technology. Pharmaceutical industry</topic><topic>Pharmacology. Drug treatments</topic><topic>Povidone - chemistry</topic><topic>Proteins</topic><topic>Proteins - administration & dosage</topic><topic>Reproduction</topic><topic>Transport</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Carr, Daniel A.</creatorcontrib><creatorcontrib>Peppas, Nicholas A.</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Engineered Materials Abstracts</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Engineering Research Database</collection><collection>Materials Research Database</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>Biotechnology Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of biomedical materials research. Part A</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Carr, Daniel A.</au><au>Peppas, Nicholas A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Assessment of poly(methacrylic acid-co-N-vinyl pyrrolidone) as a carrier for the oral delivery of therapeutic proteins using Caco-2 and HT29-MTX cell lines</atitle><jtitle>Journal of biomedical materials research. Part A</jtitle><addtitle>J. Biomed. Mater. Res</addtitle><date>2010-02</date><risdate>2010</risdate><volume>92A</volume><issue>2</issue><spage>504</spage><epage>512</epage><pages>504-512</pages><issn>1549-3296</issn><issn>1552-4965</issn><eissn>1552-4965</eissn><abstract>Hydrogels of poly(methacrylic acid‐co‐N‐vinyl pyrrolidone) were synthesized and evaluated for their use as carriers for oral protein delivery. Insulin loading efficiencies were determined to be near 90% for carriers crosslinked with ethylene glycol dimethacrylate with corresponding weight incorporation levels near 12%. Although no insulin was released in gastric conditions, as desired, near instantaneous release occurred when the pH was raised to values typical of the intestinal area. Cytocompatibility studies with Caco‐2 and Caco‐2/HT29‐MTX cultures demonstrated that microparticles did not elicit toxic effects at concentrations up to 5.0 mg/mL. Insulin transport studies revealed that the carriers did not disrupt the cell layer and thus did not change the insulin permeability in the apical‐to‐basolateral direction. Therefore, microparticles of this system were best suited for oral delivery of therapeutic agents that do not require transport facilitation. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>19213059</pmid><doi>10.1002/jbm.a.32395</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Administration, Oral Algorithms Assessments Biological and medical sciences Caco-2 Cells Carriers cell culture Cell Survival - drug effects Crosslinking cytocompatibility Drug Carriers Drug Delivery Systems Gastric Mucosa - metabolism General pharmacology Hormones. Endocrine system HT29 Cells Humans Hydrogels Hypoglycemic Agents - administration & dosage Hypoglycemic Agents - chemistry Insulin Insulin - administration & dosage Insulin - chemistry Intestinal Mucosa - metabolism Kinetics Materials Testing Medical sciences Methylmethacrylates - chemistry Microparticles Nanoparticles oral delivery Pharmaceutical technology. Pharmaceutical industry Pharmacology. Drug treatments Povidone - chemistry Proteins Proteins - administration & dosage Reproduction Transport |
title | Assessment of poly(methacrylic acid-co-N-vinyl pyrrolidone) as a carrier for the oral delivery of therapeutic proteins using Caco-2 and HT29-MTX cell lines |
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